Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease. It affects multiple systems. The disease causes considerable morbidity and mortality. Despite considerable progress in our understanding of this disease, its pathogenesis remains to be elucidate. It is well documented that both genetic and environmental factors play important roles in this disorder. It is postulated that molecular mimics may initiate an autoimmune response. The diversification of the autoimmune response with inflammation leads to end organ damage in appropriate hosts. The University of Virginia Specialized Center of Research on SLE is being established to facilitate a multidisciplinary approach to study this disease with a special emphasis on the immunological and genetic basis for it pathogenesis. The SCOR is strengthened by forming consortiums with Mayo Clinic and John Hopkins Hospital, which will provide expertise in mouse genetics, transgenic mice expressing DR and DQ antigens and the Hopkins Lupus Cohort for the proposed clinical investigation. The SCOR has four projects and three cores. The projects are 1) HLA-DR and DQ antigens in SLE-related Autoimmunity, 2) Role of T cells in Murine SLE, 3) Genetic Control of Autoimmunity in Lupus-Prone Mice and 4) Autoantibody Diversification in SLE Flares. The proposed studies are to provide experimental evidence to support the state hypothesis. The three cores are: 1) Administration Core, 2) Cell Sciences and Immunochemistry Core and 3) The Mouse Genetic Core. These cores will serve all the projects and will facilitate interactions among investigators within the UVA SCOR on SLE. The SCOR represents both inter- and intra-institutional collaborations. The interactive approach will provide new insights into the immunological and genetic factors important in SLE and may provide a rational basis for novel therapy.